The precise organization of connections within and between the cortical layers is crucial for the computations that underlie the extraordinary capabilities of the cerebral cortex. Nowhere is this more apparent than in the primary visual cortex, where the physiological response properties of neurons and the circuits they form have been described in considerable detail. One of the principal organizing features of the visual system is the presence of parallel processing streams that each carry and extract information about different features of the visual scene. The proposed studies are aimed at determining the normal sequence of events and the importance of activity in the generation of stream specific local circuits in macaque primary visual cortex. The anatomical organization of local circuits in newborn and embryonic animals will be assessed by reconstruction anterogradely-labeled axons following extracellular injections of biocytin made into coronal and tangential slices of primary visual cortex. Slices will be sectioned and double-stained for cytochrome-oxidase as well as biocytin allowing laminar and blob/interblob boundaries to be identified. Analyses of the relationships between axonal projections and laminar and blob/interblob compartments in developing animals will reveal when various functional stream-specific circuits arise and whether they emerge by the specific formation of collateral branches exclusively in correct regions or by the reorganization of initially exuberant projections. The organizational of functional local connections in developing animals will be studied using a combination of whole-cell recording and a novel caged-glutamate- based photostimulation method (Callaway and Katz 1993). This method allows the sources and strengths of connections to individual neurons to be determined. Experiments will focus on: 1) the development of connections to blob versus interblob regions of layer 2/3 originating from layers 4A, 4B, 4Calpha, and 4Cbeta, and from layer 2/3 itself, and 2) the development of layer specific projections from individual layer 6 pyramidal neurons to layers 3/4A, 4Calpha, and 4Cbeta. The influences of prenatal retinal activity and postnatal patterned visual experience on the development of these connections will be tested by depriving animals of normal activity patterns by either prenatal binocular enucleation or postnatal binocular lid suture. Results from the work proposed here will yield important insights into the mechanisms involved in the development of parallel visual processing circuits. These insights are expected to be useful for understanding the central effects of visual disorders such as strabismus and amblyopia and to aid in the development of strategies for their treatment. Dyslexia has been linked to specific anatomical and physiological deficits in the motion processing stream (Livingstone et al., 1991) and thus understand the normal development of functional stream-specific circuits and its dependence on activity may aid in understanding the cause(s) of dyslexia.